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Physiological changes in maternal glucose levels in pregnancies complicated by diabetes impact the human placental transcriptome

ABSTRACT: Physiological changes in maternal glucose levels in pregnancies complicated by diabetes impact the human placental transcriptome

PROVIDER: PRJNA1216610 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR32154135_1.fastq.gz	Fastqsanger.gz
	SRR32154135_2.fastq.gz	Fastqsanger.gz
	SRR32154139_1.fastq.gz	Fastqsanger.gz
	SRR32154139_2.fastq.gz	Fastqsanger.gz

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Physiological changes in maternal glucose levels in pregnancies complicated by diabetes impact the human placental transcriptome

Project description:Recent continuous glucose monitoring (CGM) studies have revealed that in pregnancies complicated by maternal diabetes, fluctuations in maternal glucose are linked to complications of fetal growth. The underlying mechanisms are unclear but likely involve the placenta. We cultured ex vivo human placental explants from term uncomplicated pregnancies with medium changes every 6-18 hours in variable (5/5.5 mM; normoglycaemia), or constant 5 mM (mild hypoglycaemia) or 7 mM glucose (mild hyperglycaemia) for 48 hours to recapitulate in vivo maternal glucose profiles and performed RNA sequencing. Additional placental explants were also exposed to 5.5 mM glucose.

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Placental transcriptome in pregnancies complicated by Intrauterine growth restriction (IUGR) and preeclampsia (PE)

Project description:Purpose: Identify differentially expressed genes in placental samples from early-onset (EO) IUGR, EO-PE, as well as pregnancies complicated by both EO-PE and EO-IUGR

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Placental microRNA expression in pregnancies complicated by Intrauterine growth restriction (IUGR) and preeclampsia (PE)

Project description:Purpose: Identify differentially expressed miRNAs in placental samples from early-onset (EO) IUGR, EO-PE, as well as pregnancies complicated by both EO-PE and EO-IUGR

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Placental DNA methylation in normal and complicated pregnancies

Project description:DNA methylation, a partially reversible process, is critical in tissue development and aging. The discrepancy between biological age, as estimated from methylation, and chronological age has been proposed as a potential indicator of health and disease. Epigenetic age acceleration has been implicated as a contributing mechanism in obstetric conditions such as preeclampsia and small-for-gestational-age, yet future studies could benefit from more accurate models. Herein, we curated 1,842 placental methylomes from the public domain and organized a DREAM challenge to develop models that infer gestational age. Challenge participants were blinded to the test data that we generated from 384 placentas encompassing normal and complicated pregnancies. The mean absolute error of the top performing model (0.99 weeks of gestation) and of a post-challenge placental clock model (PCPC, 1.04 weeks) compared favorably to the accuracy of existing models. Moreover, predictions obtained with new models were better calibrated across the gestational age spectrum and suggest that previous reports of accelerated aging in preterm preeclampsia were likely due to modeling artifacts. Based on predictions from previous and newly developed epigenetic models we found that accelerated placental ageing was associated with a decrease in birthweight percentiles in male neonates delivered at term in our test cohort (about 10 birthweight percentiles drop per week of age acceleration for PCPC model, p<0.001). By contrast, preterm accelerated aging was protective against delivery of a small-for-gestational-age neonate regardless of fetal sex.

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Placental transcriptome in pregnancies complicated by Intrauterine growth restriction (IUGR) and preeclampsia (PE)

Project description:Placental transcriptome in pregnancies complicated by Intrauterine growth restriction (IUGR) and preeclampsia (PE)

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Placental microRNA expression in pregnancies complicated by Intrauterine growth restriction (IUGR) and preeclampsia (PE)

Project description:Placental microRNA expression in pregnancies complicated by Intrauterine growth restriction (IUGR) and preeclampsia (PE)

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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and resulting coronavirus disease (COVID-19) causes placental dysfunction, which increases the risk of adverse pregnancy outcomes. While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare. This suggests that pathophysiology associated with maternal COVID-19, rather than direct placental infection, is responsible for placental dysfunction and alteration of the placental transcriptome. We hypothesized that maternal circulating extracellular vesicles (EVs), altered by COVID-19 during pregnancy, contribute to placental dysfunction. To examine this hypothesis, we characterized maternal circulating EVs from pregnancies complicated by COVID-19 and tested their effects on trophoblast cell physiology in vitro. We found that the gestational timing of COVID-19 is a major determinant of circulating EV function and cargo. In vitro trophoblast exposure to EVs isolated from patients with an active infection at the time of delivery, but not EVs isolated from Controls, altered key trophoblast functions including hormone production and invasion. Thus, circulating EVs from participants with an active infection, both symptomatic and asymptomatic cases, can disrupt vital trophoblast functions. EV cargo differed between participants with COVID-19 and Controls, which may contribute to the disruption of the placental transcriptome and morphology. Our findings show that COVID-19 can have effects throughout pregnancy on circulating EVs and circulating EVs are likely to participate in placental dysfunction induced by COVID-19.

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Project description:Whole-transcriptome profiles of individual human placental villi samples from twenty-five (25) Indian women with normal pregnancies during 6- to 8-weeks of gestation were examined using human whole genome expression arrays (NimbleGen 135K). The present study focused on the whole-transcriptome profiling using NimbleGen135K (070925_HG18_exp__12X135K) human whole genome expression arrays of individual human placental villi samples obtained from twenty-five (25) proven-fertile women bearing normal pregnancies voluntarily terminated between 6- and 8-weeks of gestation. Gestational age was estimated from menstrual history, physical and ultrasonographic evaluation. No case of complicated pregnancy from infection, and other significant fetal and maternal clinical indications was included. These twenty five (25) samples include biological replicates of 6, 7 and 8 weeks placental villi samples.

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Extracellular vesicles alter trophoblast function in pregnancies complicated by COVID-19

Project description:Extracellular vesicles alter trophoblast function in pregnancies complicated by COVID-19

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